Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsStarting Grant (StG), PE8, ERC-2011-StG_20101014

SummaryClimate change and the decreasing availability of fossil fuels require society to move towards sustainable and renewable resources. 2DNanoCaps will focus on electrochemical energy storage, specifically supercapacitors. In terms of performance supercapacitors fill up the gap between batteries and the classical capacitors. Whereas batteries possess a high energy density but low power density, supercapacitors possess high power density but low energy density. Efforts are currently dedicated to move supercapacitors towards high energy density and high power density performance. Improvements have been achieved in the last few years due to the use of new electrode nanomaterials and the design of new hybrid faradic/capacitive systems. We recognize, however, that we are reaching a newer limit beyond which we will only see small incremental improvements. The main reason for this being the intrinsic difficulty in handling and processing materials at the nano-scale and the lack of communication across different scientific disciplines. I plan to use a multidisciplinary approach, where novel nanomaterials, existing knowledge on nano-scale processing and established expertise in device fabrication and testing will be brought together to focus on creating more efficient supercapacitor technologies. 2DNanoCaps will exploit liquid phase exfoliated two-dimensional nanomaterials such as transition metal oxides, layered metal chalcogenides and graphene as electrode materials. Electrodes will be ultra-thin (capacitance and thickness of the electrodes are inversely proportional), conductive, with high dielectric constants. Intercalation of ions between the assembled 2D flakes will be also achievable, providing pseudo-capacitance. The research here proposed will be initially based on fundamental laboratory studies, recognising that this holds the key to achieving step-change in supercapacitors, but also includes scaling-up and hybridisation as final objectives.

Climate change and the decreasing availability of fossil fuels require society to move towards sustainable and renewable resources. 2DNanoCaps will focus on electrochemical energy storage, specifically supercapacitors. In terms of performance supercapacitors fill up the gap between batteries and the classical capacitors. Whereas batteries possess a high energy density but low power density, supercapacitors possess high power density but low energy density. Efforts are currently dedicated to move supercapacitors towards high energy density and high power density performance. Improvements have been achieved in the last few years due to the use of new electrode nanomaterials and the design of new hybrid faradic/capacitive systems. We recognize, however, that we are reaching a newer limit beyond which we will only see small incremental improvements. The main reason for this being the intrinsic difficulty in handling and processing materials at the nano-scale and the lack of communication across different scientific disciplines. I plan to use a multidisciplinary approach, where novel nanomaterials, existing knowledge on nano-scale processing and established expertise in device fabrication and testing will be brought together to focus on creating more efficient supercapacitor technologies. 2DNanoCaps will exploit liquid phase exfoliated two-dimensional nanomaterials such as transition metal oxides, layered metal chalcogenides and graphene as electrode materials. Electrodes will be ultra-thin (capacitance and thickness of the electrodes are inversely proportional), conductive, with high dielectric constants. Intercalation of ions between the assembled 2D flakes will be also achievable, providing pseudo-capacitance. The research here proposed will be initially based on fundamental laboratory studies, recognising that this holds the key to achieving step-change in supercapacitors, but also includes scaling-up and hybridisation as final objectives.

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsConsolidator Grant (CoG), PE8, ERC-2015-CoG

SummaryMy vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices.
Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies.
3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.

My vision is to establish, within the framework of an ERC CoG, a multidisciplinary group which will work in concert towards pioneering the integration of novel 2-Dimensional nanomaterials with novel additive fabrication techniques to develop a unique class of energy storage devices.
Batteries and supercapacitors are two very complementary types of energy storage devices. Batteries store much higher energy densities; supercapacitors, on the other hand, hold one tenth of the electricity per unit of volume or weight as compared to batteries but can achieve much higher power densities. Technology is currently striving to improve the power density of batteries and the energy density of supercapacitors. To do so it is imperative to develop new materials, chemistries and manufacturing strategies.
3D2DPrint aims to develop micro-energy devices (both supercapacitors and batteries), technologies particularly relevant in the context of the emergent industry of micro-electro-mechanical systems and constantly downsized electronics. We plan to use novel two-dimensional (2D) nanomaterials obtained by liquid-phase exfoliation. This method offers a new, economic and easy way to prepare ink of a variety of 2D systems, allowing to produce wide device performance window through elegant and simple constituent control at the point of fabrication. 3D2DPrint will use our expertise and know-how to allow development of advanced AM methods to integrate dissimilar nanomaterial blends and/or “hybrids” into fully embedded 3D printed energy storage devices, with the ultimate objective to realise a range of products that contain the above described nanomaterials subcomponent devices, electrical connections and traditional micro-fabricated subcomponents (if needed) ideally using a single tool.

Max ERC Funding

2 499 942 €

Duration

Start date: 2016-10-01, End date: 2021-09-30

Project acronymActive-DNA

ProjectComputationally Active DNA Nanostructures

Researcher (PI)Damien WOODS

Host Institution (HI)NATIONAL UNIVERSITY OF IRELAND MAYNOOTH

Call DetailsConsolidator Grant (CoG), PE6, ERC-2017-COG

SummaryDuring the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab.
The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.

During the 20th century computer technology evolved from bulky, slow, special purpose mechanical engines to the now ubiquitous silicon chips and software that are one of the pinnacles of human ingenuity. The goal of the field of molecular programming is to take the next leap and build a new generation of matter-based computers using DNA, RNA and proteins. This will be accomplished by computer scientists, physicists and chemists designing molecules to execute ``wet'' nanoscale programs in test tubes. The workflow includes proposing theoretical models, mathematically proving their computational properties, physical modelling and implementation in the wet-lab.
The past decade has seen remarkable progress at building static 2D and 3D DNA nanostructures. However, unlike biological macromolecules and complexes that are built via specified self-assembly pathways, that execute robotic-like movements, and that undergo evolution, the activity of human-engineered nanostructures is severely limited. We will need sophisticated algorithmic ideas to build structures that rival active living systems. Active-DNA, aims to address this challenge by achieving a number of objectives on computation, DNA-based self-assembly and molecular robotics. Active-DNA research work will range from defining models and proving theorems that characterise the computational and expressive capabilities of such active programmable materials to experimental work implementing active DNA nanostructures in the wet-lab.

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsStarting Grant (StG), PE8, ERC-2011-StG_20101014

Summary1.2 billion people worldwide lack access to safe drinking water. Drinking water quality is threatened by newly emerging organic micro-pollutants (pesticides, pharmaceuticals, industrial chemicals) in source waters. Nanofiltration is a technology that is expected to play a key role in future water treatment processes due to its effectiveness in removal of micropollutants. However, the loss of membrane flux due to fouling is one of the main impediments in the development of membrane processes for use in drinking water treatment. Currently there is a wholly inadequate mechanistic understanding of the role of biofilm on the fouling of nanofiltration membranes.
Applying techniques including confocal microscopy, force spectroscopy, and infrared spectroscopy using an experimental programme informed by a technique known as scale-down together with mathematical modelling, it is confidently expected that significant advances will be gained in the mechanistic understanding of nanofiltration biofouling.
The specific objectives are 1. How is the rate of formation and extent of such biofilms influenced by the biological response to the local microenvironment? 2 Elucidate the effect of extracellular polysaccharide substances on physical properties, composition and structure of these biofilms. 3: Investigate mechanisms to enhance biofilm removal by a physical detachment process complemented by techniques that alter biofilm material properties.
A more fundamental insight into the mechanisms of nanofiltration operation will help in further development of this treatment method in future water treatment processes.

1.2 billion people worldwide lack access to safe drinking water. Drinking water quality is threatened by newly emerging organic micro-pollutants (pesticides, pharmaceuticals, industrial chemicals) in source waters. Nanofiltration is a technology that is expected to play a key role in future water treatment processes due to its effectiveness in removal of micropollutants. However, the loss of membrane flux due to fouling is one of the main impediments in the development of membrane processes for use in drinking water treatment. Currently there is a wholly inadequate mechanistic understanding of the role of biofilm on the fouling of nanofiltration membranes.
Applying techniques including confocal microscopy, force spectroscopy, and infrared spectroscopy using an experimental programme informed by a technique known as scale-down together with mathematical modelling, it is confidently expected that significant advances will be gained in the mechanistic understanding of nanofiltration biofouling.
The specific objectives are 1. How is the rate of formation and extent of such biofilms influenced by the biological response to the local microenvironment? 2 Elucidate the effect of extracellular polysaccharide substances on physical properties, composition and structure of these biofilms. 3: Investigate mechanisms to enhance biofilm removal by a physical detachment process complemented by techniques that alter biofilm material properties.
A more fundamental insight into the mechanisms of nanofiltration operation will help in further development of this treatment method in future water treatment processes.

Max ERC Funding

1 468 987 €

Duration

Start date: 2011-10-01, End date: 2016-09-30

Project acronymASTROFLOW

ProjectThe influence of stellar outflows on exoplanetary mass loss

Researcher (PI)Aline VIDOTTO

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsConsolidator Grant (CoG), PE9, ERC-2018-COG

SummaryASTROFLOW aims to make ground-breaking progress in our physical understanding of exoplanetary mass loss, by quantifying the influence of stellar outflows on atmospheric escape of close-in exoplanets. Escape plays a key role in planetary evolution, population, and potential to develop life. Stellar irradiation and outflows affect planetary mass loss: irradiation heats planetary atmospheres, which inflate and more likely escape; outflows cause pressure confinement around otherwise freely escaping atmospheres. This external pressure can increase, reduce or even suppress escape rates; its effects on exoplanetary mass loss remain largely unexplored due to the complexity of such interactions. I will fill this knowledge gap by developing a novel modelling framework of atmospheric escape that will, for the first time, consider the effects of realistic stellar outflows on exoplanetary mass loss. My expertise in stellar wind theory and 3D magnetohydrodynamic simulations is crucial for producing the next-generation models of planetary escape. My framework will consist of state-of-the-art, time-dependent, 3D simulations of stellar outflows (Method 1), which will be coupled to novel 3D simulations of atmospheric escape (Method 2). My models will account for the major underlying physical processes of mass loss. With this, I will determine the response of planetary mass loss to realistic stellar particle, magnetic and radiation environments and will characterise the physical conditions of the escaping material. I will compute how its extinction varies during transit and compare synthetic line profiles to atmospheric escape observations from, eg, Hubble and our NASA cubesat CUTE. Strong synergy with upcoming observations (JWST, TESS, SPIRou, CARMENES) also exists. Determining the lifetime of planetary atmospheres is essential to understanding populations of exoplanets. ASTROFLOW’s work will be the foundation for future research of how exoplanets evolve under mass-loss processes.

ASTROFLOW aims to make ground-breaking progress in our physical understanding of exoplanetary mass loss, by quantifying the influence of stellar outflows on atmospheric escape of close-in exoplanets. Escape plays a key role in planetary evolution, population, and potential to develop life. Stellar irradiation and outflows affect planetary mass loss: irradiation heats planetary atmospheres, which inflate and more likely escape; outflows cause pressure confinement around otherwise freely escaping atmospheres. This external pressure can increase, reduce or even suppress escape rates; its effects on exoplanetary mass loss remain largely unexplored due to the complexity of such interactions. I will fill this knowledge gap by developing a novel modelling framework of atmospheric escape that will, for the first time, consider the effects of realistic stellar outflows on exoplanetary mass loss. My expertise in stellar wind theory and 3D magnetohydrodynamic simulations is crucial for producing the next-generation models of planetary escape. My framework will consist of state-of-the-art, time-dependent, 3D simulations of stellar outflows (Method 1), which will be coupled to novel 3D simulations of atmospheric escape (Method 2). My models will account for the major underlying physical processes of mass loss. With this, I will determine the response of planetary mass loss to realistic stellar particle, magnetic and radiation environments and will characterise the physical conditions of the escaping material. I will compute how its extinction varies during transit and compare synthetic line profiles to atmospheric escape observations from, eg, Hubble and our NASA cubesat CUTE. Strong synergy with upcoming observations (JWST, TESS, SPIRou, CARMENES) also exists. Determining the lifetime of planetary atmospheres is essential to understanding populations of exoplanets. ASTROFLOW’s work will be the foundation for future research of how exoplanets evolve under mass-loss processes.

Max ERC Funding

1 999 956 €

Duration

Start date: 2019-09-01, End date: 2024-08-31

Project acronymBioWater

ProjectDevelopment of new chemical imaging techniques to understand the function of water in biocompatibility, biodegradation and biofouling

Researcher (PI)Aoife Ann Gowen

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsStarting Grant (StG), PE8, ERC-2013-StG

SummaryWater is the first molecule to come into contact with biomaterials in biological systems and thus essential to the processes of biodegradation, biocompatibility and biofouling. Despite this fact, little is currently known about how biomaterials interact with water. This knowledge is crucial for the development and optimisation of novel functional biomaterials for human health (e.g. biosensing devices, erodible biomaterials, drug release carriers, wound dressings). BioWater will develop near and mid infrared chemical imaging (NIR-MIR-CI) techniques to investigate the fundamental interaction between biomaterials and water in order to understand the key processes of biodegradation, biocompatibility and biofouling. This ambitious yet achievable project will focus on two major categories of biomaterials relevant to human health: extracellular collagens and synthetic biopolymers. Initially, interactions between these biomaterials and water will be investigated; subsequently interactions with more complicated matrices (e.g. protein solutions and cellular systems) will be studied. CI data will be correlated with standard surface characterization, biocompatibility and biodegradation measurements. Molecular dynamic simulations will complement this work to identify the most probable molecular structures of water at different biomaterial interfaces.
Advanced understanding of the role of water in biocompatibility, biofouling and biodegradation processes will facilitate the optimization of biomaterials tailored to specific cellular environments with a broad range of therapeutic applications (e.g. drug eluting stents, tissue engineering, wound healing). The new NIR-MIR-CI/chemometric methodologies developed in BioWater will allow for the rapid characterization and monitoring of novel biomaterials at pre-clinical stages, improving process control by overcoming the laborious and time consuming large-scale sampling methods currently required in biomaterials development.

Water is the first molecule to come into contact with biomaterials in biological systems and thus essential to the processes of biodegradation, biocompatibility and biofouling. Despite this fact, little is currently known about how biomaterials interact with water. This knowledge is crucial for the development and optimisation of novel functional biomaterials for human health (e.g. biosensing devices, erodible biomaterials, drug release carriers, wound dressings). BioWater will develop near and mid infrared chemical imaging (NIR-MIR-CI) techniques to investigate the fundamental interaction between biomaterials and water in order to understand the key processes of biodegradation, biocompatibility and biofouling. This ambitious yet achievable project will focus on two major categories of biomaterials relevant to human health: extracellular collagens and synthetic biopolymers. Initially, interactions between these biomaterials and water will be investigated; subsequently interactions with more complicated matrices (e.g. protein solutions and cellular systems) will be studied. CI data will be correlated with standard surface characterization, biocompatibility and biodegradation measurements. Molecular dynamic simulations will complement this work to identify the most probable molecular structures of water at different biomaterial interfaces.
Advanced understanding of the role of water in biocompatibility, biofouling and biodegradation processes will facilitate the optimization of biomaterials tailored to specific cellular environments with a broad range of therapeutic applications (e.g. drug eluting stents, tissue engineering, wound healing). The new NIR-MIR-CI/chemometric methodologies developed in BioWater will allow for the rapid characterization and monitoring of novel biomaterials at pre-clinical stages, improving process control by overcoming the laborious and time consuming large-scale sampling methods currently required in biomaterials development.

SummaryThis program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation.
Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact.
This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.

This program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation.
Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact.
This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.

Max ERC Funding

1 372 135 €

Duration

Start date: 2017-10-01, End date: 2022-09-30

Project acronymBONEMECHBIO

ProjectFrontier research in bone mechanobiology during normal physiology, disease and for tissue regeneration

Researcher (PI)Laoise Maria Cunningham

Host Institution (HI)NATIONAL UNIVERSITY OF IRELAND GALWAY

Call DetailsStarting Grant (StG), PE8, ERC-2010-StG_20091028

SummaryWhile previous studies have investigated cell-signalling pathways that facilitate mechanotransduction and have provided a wealth of data, to date, in vivo mechanobiology is not fully understood. In the research study proposed the applicant will embark upon frontier research to delineate these specific aspects of bone mechanotransduction during normal physiology, disease and for tissue regeneration purposes. If these quantities were better understood the proposed research program will deliver significant advances in the understanding of the mechanical regulation of bone remodelling during normal physiology and osteoporosis, and will enhance approaches for regeneration of bone tissue for treatment of bone pathologies. The primary objective is to delineate the normal mechanosensory and signalling mechanisms of bone cells. The secondary objective is to determine whether the regulatory role of bone cells is inhibited or impaired during bone diseases such as osteoporosis. The final objective of this project is to develop an in vitro mechanical loading device that can enhance bone tissue regeneration and thereby advance current treatment approaches for bone pathologies. To address these objectives, five hypotheses have been defined, each of which will underpin the research of five work packages. A combination of experimental studies, using animal models and in vitro cell culture, and computational modelling will be taken to test each of these hypotheses. Answering these hypotheses will bring us closer to an understanding of the origins of bone mechanobiology and diseases such as osteoporosis. Furthermore, the results of these studies will facilitate development of novel approaches to enhance bone regeneration in vitro.

While previous studies have investigated cell-signalling pathways that facilitate mechanotransduction and have provided a wealth of data, to date, in vivo mechanobiology is not fully understood. In the research study proposed the applicant will embark upon frontier research to delineate these specific aspects of bone mechanotransduction during normal physiology, disease and for tissue regeneration purposes. If these quantities were better understood the proposed research program will deliver significant advances in the understanding of the mechanical regulation of bone remodelling during normal physiology and osteoporosis, and will enhance approaches for regeneration of bone tissue for treatment of bone pathologies. The primary objective is to delineate the normal mechanosensory and signalling mechanisms of bone cells. The secondary objective is to determine whether the regulatory role of bone cells is inhibited or impaired during bone diseases such as osteoporosis. The final objective of this project is to develop an in vitro mechanical loading device that can enhance bone tissue regeneration and thereby advance current treatment approaches for bone pathologies. To address these objectives, five hypotheses have been defined, each of which will underpin the research of five work packages. A combination of experimental studies, using animal models and in vitro cell culture, and computational modelling will be taken to test each of these hypotheses. Answering these hypotheses will bring us closer to an understanding of the origins of bone mechanobiology and diseases such as osteoporosis. Furthermore, the results of these studies will facilitate development of novel approaches to enhance bone regeneration in vitro.

Max ERC Funding

1 499 911 €

Duration

Start date: 2011-02-01, End date: 2016-01-31

Project acronymCARBENZYMES

ProjectProbing the relevance of carbene binding motifs in enzyme reactivity

Researcher (PI)Martin Albrecht

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsStarting Grant (StG), PE4, ERC-2007-StG

SummaryHistidine (His) is an ubiquitous ligand in the active site of metalloenzymes that is assumed by default to bind the metal center through one of its nitrogen atoms. However, protonation of His, which is likely to occur in locally slightly acidic environment, gives imidazolium sites that can bind a metal in a carbene-type structure as found in N-heterocyclic carbene complexes. Such carbene bonding has a dramatic effect on the properties of the metal center and may provide a rational for the mode of action of metalloenzymes that are still lacking a solid understanding. Up to now, the possibility of carbene bonding has been completely overlooked. Hence, any evidence for such His coordination via carbon will induce a shift of paradigm in classical peptide chemistry and will be directly included in basic textbooks. Moreover, this unprecedented bonding mode will provide access to unique and hitherto unknown reactivity patterns for artificial enzyme mimics. Undoubtedly, such a break-through will set a new stage in modern metalloenzyme research. A multicentered approach is proposed to identify for the first time carbene bonding in enzymes. This approach unconventionally combines the current frontiers of organometallic and biochemical knowledge and hence crosses traditional boarders. Specifically, we aim at probing carbene bonding of His by identifying reactivity patterns that are selective for metal-carbenes but not for metal-imine complexes. This will allow for efficient screening of large classes of metalloenzymes. In parallel, active site models will be constructed in which the His ligand is substituted by a heterocyclic carbene as a rigidly C-bonding His analog. For this purpose chemical synthesis will be considered as well as enzyme mutagenesis and subsequent carbene coordination. While such new bioorganometallic entities will be highly attractive to probe the influence of C-bound His on the metal site, they also provide conceputally new types of versatile catalysts.

Histidine (His) is an ubiquitous ligand in the active site of metalloenzymes that is assumed by default to bind the metal center through one of its nitrogen atoms. However, protonation of His, which is likely to occur in locally slightly acidic environment, gives imidazolium sites that can bind a metal in a carbene-type structure as found in N-heterocyclic carbene complexes. Such carbene bonding has a dramatic effect on the properties of the metal center and may provide a rational for the mode of action of metalloenzymes that are still lacking a solid understanding. Up to now, the possibility of carbene bonding has been completely overlooked. Hence, any evidence for such His coordination via carbon will induce a shift of paradigm in classical peptide chemistry and will be directly included in basic textbooks. Moreover, this unprecedented bonding mode will provide access to unique and hitherto unknown reactivity patterns for artificial enzyme mimics. Undoubtedly, such a break-through will set a new stage in modern metalloenzyme research. A multicentered approach is proposed to identify for the first time carbene bonding in enzymes. This approach unconventionally combines the current frontiers of organometallic and biochemical knowledge and hence crosses traditional boarders. Specifically, we aim at probing carbene bonding of His by identifying reactivity patterns that are selective for metal-carbenes but not for metal-imine complexes. This will allow for efficient screening of large classes of metalloenzymes. In parallel, active site models will be constructed in which the His ligand is substituted by a heterocyclic carbene as a rigidly C-bonding His analog. For this purpose chemical synthesis will be considered as well as enzyme mutagenesis and subsequent carbene coordination. While such new bioorganometallic entities will be highly attractive to probe the influence of C-bound His on the metal site, they also provide conceputally new types of versatile catalysts.

Max ERC Funding

1 249 808 €

Duration

Start date: 2008-07-01, End date: 2013-06-30

Project acronymChemLife

ProjectArtificial micro-vehicles with life-like behaviour

Researcher (PI)Larisa FLOREA

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsStarting Grant (StG), PE5, ERC-2018-STG

SummaryOne of the most interesting properties of living organisms is the way in which they can sense and respond to changes by moving. Movement has been essential to the survival of all life; even units as small as cells can react to different chemicals through movement. This is a phenomenon known as chemotaxis. Bacteria use chemotaxis to find sources of food, while white blood cells use chemotaxis to follow a chemical trail left by a virus, then find it and destroy it. Throughout areas of science, from robotics to drug delivery, if we could mimic a fraction of this fascinating complexity, the possibilities would be endless.
Imagine micro-structured vehicles, which could ‘navigate’ through complex fluidic environments, and could effectively ‘recognise’, ‘sense’, ‘diagnose’ and ‘treat’ a variety of conditions. This is exactly what this proposed project, ChemLife, will explore. I will make smart droplets which travel through complicated mazes by chemotaxis, communicate with each other, and move to find their partners or locate and neutralise a ‘droplet intruder’. Other biological systems have much more complicated means of movement, such as swimming, crawling or gliding along surfaces. In an attempt to replicate this, I will fabricate ‘swimmers’ and ‘crawlers’, from soft materials which will move independently and travel through liquids or at the bottom of fluidic channels. Not only will these micro-vehicles be able to travel inside fluids, but they will also be able to detect molecules, signal to other vehicles, and repair problems which they encounter. They underpin a key ambition of ChemLife: the realisation of a Biomimetic Toolbox, a library of adaptable vehicles, which can be demonstrated in a wide range of scenarios. The assembly of these micro-vehicles in to ‘smart’ societies which can perform complicated tasks would be a really exciting achievement, with the potential to become a disruptive foundational breakthrough for movement and transport at the micro-scale.

One of the most interesting properties of living organisms is the way in which they can sense and respond to changes by moving. Movement has been essential to the survival of all life; even units as small as cells can react to different chemicals through movement. This is a phenomenon known as chemotaxis. Bacteria use chemotaxis to find sources of food, while white blood cells use chemotaxis to follow a chemical trail left by a virus, then find it and destroy it. Throughout areas of science, from robotics to drug delivery, if we could mimic a fraction of this fascinating complexity, the possibilities would be endless.
Imagine micro-structured vehicles, which could ‘navigate’ through complex fluidic environments, and could effectively ‘recognise’, ‘sense’, ‘diagnose’ and ‘treat’ a variety of conditions. This is exactly what this proposed project, ChemLife, will explore. I will make smart droplets which travel through complicated mazes by chemotaxis, communicate with each other, and move to find their partners or locate and neutralise a ‘droplet intruder’. Other biological systems have much more complicated means of movement, such as swimming, crawling or gliding along surfaces. In an attempt to replicate this, I will fabricate ‘swimmers’ and ‘crawlers’, from soft materials which will move independently and travel through liquids or at the bottom of fluidic channels. Not only will these micro-vehicles be able to travel inside fluids, but they will also be able to detect molecules, signal to other vehicles, and repair problems which they encounter. They underpin a key ambition of ChemLife: the realisation of a Biomimetic Toolbox, a library of adaptable vehicles, which can be demonstrated in a wide range of scenarios. The assembly of these micro-vehicles in to ‘smart’ societies which can perform complicated tasks would be a really exciting achievement, with the potential to become a disruptive foundational breakthrough for movement and transport at the micro-scale.